Ocular Surface最新文献

Purpose

This study aimed to analyze the differences in the expression of pain-related genes in conjunctival epithelial cells among symptomatic contact lens (CL) wearers (SCLWs), asymptomatic CL wearers (ACLWs), and non-CL wearers (non-CLWs).

Methods

For this study, 60 participants (20 non-CLWs, 40 CLWs) were enrolled. The CLW group comprised 20 ACLWs and 20 SCLWs according to the Contact Lens Dry Eye Questionnaire short form©. Conjunctival cells were collected using impression cytology, and RNA was isolated and used to determine the expression levels of 85 human genes involved in neuropathic and inflammatory pain. The effects of CL wear and discomfort were evaluated using mixed-effects ANOVA with partially nested fixed-effects model. Gene set enrichment analysis was performed to assign biological meaning to sets of differentially expressed genes.

Results

Six genes (CD200, EDN1, GRIN1, PTGS1, P2RX7, and TNF) were significantly upregulated in CLWs compared to non-CLWs. Eleven genes (ADORA1, BDKRB1, CACNA1B, DBH, GRIN1, GRM1, HTR1A, PDYN, PTGS1, P2RX3, and TNF) were downregulated in SCLWs compared to ACLWs. These genes were mainly related to pain, synaptic transmission and signaling, ion transport, calcium transport and concentration, and cell-cell signaling.

Conclusions

CL wear modified the expression of pain- and inflammation-related genes in conjunctival epithelial cells. These changes may be in part, along with other mechanisms, responsible for CL discomfort in SCLWs.

Purpose

Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear.

Methods

In this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, dorsal root and trigeminal ganglia with the changes in the ocular surface, including tear proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production.

Results

The lacrimal gland, conjunctival goblet cells and cornea showed morphological changes along with alterations in tear proteins without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and Pigr in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating chemokines.

Conclusion

The early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment could delay or even prevent the ocular complications of DM such as DED and PN.

Purpose

Tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) is upregulated in various pathophysiological contexts, where it has a diverse repertoire of immunoregulatory functions. Herein, we investigated the expression and function of TSG-6 during corneal homeostasis and after injury.

Methods

Human corneas, eyeballs from BALB/c (TSG-6^+/+), TSG-6^+/− and TSG-6^−/− mice, human immortalized corneal epithelial cells and murine corneal epithelial progenitor cells were prepared for immunostaining and real time PCR analysis of endogenous expression of TSG-6. Mice were subjected to unilateral corneal debridement or alkali burn (AB) injuries and wound healing assessed over time using fluorescein stain, in vivo confocal microscopy and histology.

Results

TSG-6 is endogenously expressed in the human and mouse cornea and established corneal epithelial cell lines and is upregulated after injury. A loss of TSG-6 has no structural and functional effect in the cornea during homeostasis. No differences were noted in the rate of corneal epithelial wound closure between BALB/c, TSG-6^+/− and TSG-6^−/− mice. TSG-6^−/− mice presented decreased inflammatory response within the first 24 h of injury and accelerated corneal wound healing following AB when compared to control mice.

Conclusion

TSG-6 is endogenously expressed in the cornea and upregulated after injury where it propagates the inflammatory response following chemical injury.

Purpose

The study investigated effectiveness of a novel PEDF peptide mimetic to alleviate dry eye-like pathologies in a Type I diabetic mouse model established using streptozotocin.

Methods

Mice were treated topically for 3–6 weeks with Ppx (a 17-mer PEDF mimetic) 2x/day or vehicle. Corneal sensitivity, tear film, epithelial and endothelial injury were measured using Cochet-Bonnet esthesiometer, phenol red cotton thread wetting, fluorescein sodium staining, and ZO1 expression, respectively. Inflammatory and parasympathetic nerve markers and activation of the MAPK/JNK pathways in the lacrimal glands were measured.

Results

Diabetic mice exhibited features of dry eye including reduced corneal sensation and tear secretion and increased corneal epithelium injury, nerve degeneration, and edema. Ppx reversed these pathologies and restored ZO1 expression and morphological integrity of the endothelium. Upregulation of IL-1β and TNFα, increased activation of P-38, JNK, and ERK, and higher levels of M3ACHR in diabetic lacrimal glands were also reversed by the peptide treatment.

Conclusion

The study demonstrates that topical application of a synthetic PEDF mimetic effectively alleviates diabetes-induced dry eye by restoring corneal sensitivity, tear secretion, and endothelial barrier and lacrimal gland function. These findings have significant implications for the potential treatment of dry eye using a cost-effective and reproducible approach with minimal invasiveness and no obvious side effects.

Dry eye disease (DED), a multifactorial ocular disease that significantly impacts quality of life, is most commonly reported in adults. This review describes the prevalence, risk factors, diagnosis and management of DED in children. A literature search, conducted from January 2000–December 2022, identified 54 relevant publications. Using similar diagnostic criteria to those reported in adults, namely standardized questionnaires and evaluation of tear film homeostatic signs, the prevalence of DED in children ranged from 5.5% to 23.1 %. There was limited evidence for the influence of ethnicity in children, however some studies reported an effect of sex in older children. Factors independently associated with DED included digital device use, duration of digital device use, outdoor time and urban living, Rates of DED were higher in children with ocular allergy and underlying systemic diseases. Compared with similar studies in adults, the prevalence of a prior DED diagnosis or a diagnosis based on signs and symptoms was lower in children, but symptoms were commonly reported. Treatment options were similar to those in adults, including lifestyle modifications, blinking, management of lid disease and unpreserved lubricants in mild disease with escalating treatment with severity. Management requires careful exploration of symptoms, medical history and the diagnosis and management of ocular comorbidities such as allergy and anterior blepharitis. Appropriately powered population-based studies are required to understand the prevalence of and risk factors for DED in children. Development of age-appropriate thresholds for signs and symptoms of DED would support better diagnosis of disease and understanding of natural history.

Purpose

This double-blinded randomized clinical trial aimed to evaluate the efficacy of injecting allogeneic adipose-derived mesenchymal stem cells (ASCs) into the lacrimal gland (LG) for the treatment of dry eye disease (DED) secondary to Sjögren's syndrome (SS).

Methods

Fifty-four participants with severe DED secondary to SS were included and allocated to either ASCs (n = 20), vehicle (n = 20), or a non-randomized observation group (n = 14). The intervention groups received a single injection of either ASCs or an active comparator (vehicle, Cryostor® CS10) into the LG in one eye, while the observation group received lubricating eye drops only. The primary outcome measure was changes in Ocular Surface Disease Index (OSDI) score and secondary outcome measures were non-invasive tear break-up time, tear meniscus height, Schirmer's test, and Oxford score within a 12-month follow-up.

Results

A significant reduction in OSDI score was observed in the ASCs and vehicle groups compared to the observation group. In addition, the ASCs group demonstrated a significant increase in non-invasive tear break-up time compared to the vehicle group at the 4-week follow-up and to the observation group at the 12-month follow-up. A significant improvement in ocular surface staining, tear osmolarity, and Schirmer test score from baseline was also observed in the ASCs group; however, these changes were not significant compared to the other groups.

Conclusion

Improvement of subjective and objective signs and symptoms of DED was observed in both intervention groups following injection into the LG compared to the observation group. Future studies should investigate the mode-of-action of both injection treatments.

Purpose

To study the outcomes of topical Retinol Palmitate ophthalmic solution in chronic Stevens-Johnson Syndrome with ocular surface keratinisation.

Methods

It was a comparative interventional study conducted at Rajendra Prasad Centre for Ophthalmic Sciences, Delhi, India from 2020 to 2022 evaluating outcomes of addition of topical Retinol Palmitate to conventional treatment objectively as well as subjectively from baseline up to 12 weeks.

Results

A statistically significant improvement was seen in patients who received topical Retinol palmitate at 12 weeks in terms of Schirmer-1 test(p=<0.01), tear prism height on ASOCT(p = 0.02), Rose Bengal staining score of cornea(p = 0.01) and conjunctiva (p < 0.01), reduction of ocular surface keratinisation on impression cytology(p = 0.01) and subjective evaluation using OSDI questionnaire(p = 0.04).Impression cytology revealed goblet cells in Retinol palmitate group at 1 week after initiation of therapy, which increased further at 1 month follow up but reduced at 3 months. No goblet cells were seen in control group at any follow-up. No significant difference was noted between the two groups in terms of visual acuity, tear film breakup time, inflammatory cells on impression cytology and inflammatory markers in tears.

Conclusion

Topical Retinol palmitate is a safe and effective drug in cases of chronic SJS with ocular surface keratinisation. It has the potential to reverse keratinisation of the ocular surface and promote development of goblet cells. However, the survival of goblet cells is not long lasting.

Background

Meibomian gland dysfunction (MGD) is one of the most common conditions in ophthalmic practice and the most frequent cause of evaporative dry eye disease (DED). However, the immune mechanisms leading to this pathology are not fully understood and the diagnostic tests available are limited. Here, we used the nCounter technology to analyze immune gene expression in DED-MGD that can be used for developing diagnostic signatures for DED.

Methods

Conjunctival cell samples were obtained by aspiration from patients with DED-MGD (n = 27) and asymptomatic controls (n = 22). RNA was purified, converted to cDNA, preamplified and analyzed using the Gene Expression Human Immune V2 panel (NanoString), which includes 579 target and 15 housekeeping genes. A machine learning (ML) algorithm was applied to design a signature associated with DED-MGD.

Results

Forty-five immune genes were found upregulated in DED-MGD vs. controls, involved in eight signaling pathways, IFN I/II, MHC class I/II, immunometabolism, B cell receptor, T Cell receptor, and T helper-17 (Th-17) differentiation. Additionally, statistically significant correlations were found between 31 genes and clinical characteristics of the disease such as lid margin or tear osmolarity (Pearson's r < 0.05). ML analysis using a recursive feature elimination (RFE) algorithm selected a 4-gene mRNA signature that discriminated DED-MGD from control samples with an area under the ROC curve (AUC ROC) of 0.86 and an accuracy of 77.5%.

Conclusions

Multiplexed mRNA analysis of conjunctival cells can be used to analyze immune gene expression patterns in patients with DED-MGD and to generate diagnostic signatures.